Inclusion Criteria:
* Ability to understand and willingness to sign an informed consent form
* Ability to adhere to the study visit schedule and other protocol requirements
* Patients must have histologically or cytologically confirmed prostate cancer that is clinically localized as defined by negative cross-section imaging and/or bone scan, and classified as high or very high risk per National Comprehensive Cancer Network (NCCN) guideline
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1
* Life expectancy \>= 10 years
* Men who have selected radical prostatectomy as the primary treatment for their prostate cancer
* Prostate cancer tumors with alterations in key DNA repair genes. This will include at least one alteration in a gene involved in DNA repair primarily through the homologous recombination pathway including BRCA1/2, ATM, CHEK1/2 FANCA, FANCD2, FANCL, GEN1, NBN, PALB2, RAD51, RAD51c, and BRIP1. Mutations will be selected that are known or likely pathogenic. Mean allele frequencies will be assessed to estimate mono versus biallelic loss of function. Patients with biallelic deletions or mutations will be prioritized for inclusion to make up at least 30% of the enrollment (i.e., 10 patients) to gauge response in this group over monoallelic loss. Final inclusion will be determined by the principal investigator
* Must be able to swallow whole capsules
* To avoid risk of drug exposure through the ejaculate, male subjects (even if they have undergone a successful vasectomy) must agree while on study therapy (including during dose interruptions) and for 3 months following the last dose of study drug to:
* Use a condom during sexual activity or practice complete sexual abstinence
* Not donate sperm
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (obtained =\< 14 days of the first study treatment)
* Platelet count \>= 100 x 10\^9/L (obtained =\< 14 days of the first study treatment)
* Hemoglobin \>= 9 g/dL (may have been transfused) (obtained =\< 14 days of the first study treatment)
* Total bilirubin level =\< 1.5 x the upper limit of normal (ULN) range (obtained =\< 14 days of the first study treatment)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =\< 2.5 x ULN or AST and ALT levels =\< 5 x ULN (for subjects with documented metastatic disease to the liver) (obtained =\< 14 days of the first study treatment)
* International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (for patients on anticoagulation they must be receiving a stable dose for at least 1 week prior to randomization) (obtained =\< 14 days of the first study treatment)
* Creatinine clearance \> 30 mL/min by Cockcroft-Gault formula (or local institutional standard method) (obtained =\< 14 days of the first study treatment)
Exclusion Criteria:
* Any condition that would prohibit the understanding or rendering of informed consent
* Prior treatment for prostate cancer
* Prior treatment with a PARP inhibitor
* Prior treatment with androgen deprivation therapy (luteinizing hormone-releasing hormone \[LHRH\] agonist/antagonist), antiandrogen (e.g., bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g., abiraterone, orteronel)
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
* Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient's safety or compliance on trial
* Severe infection that in the opinion of the investigator would interfere with the patient's safety or compliance on trial within 4 weeks prior to enrollment
* Known allergies, hypersensitivity, or intolerance to niraparib or its excipients (refer to investigator's brochure)
* Known disorder affecting gastrointestinal absorption
* Corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiography (ECG) \> 450 msec
* Receiving concomitant medications that prolong QTc and are unable to discontinue use while receiving study drug
* History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
* Known human immunodeficiency virus (HIV) positive subjects with 1 or more of the following:
* Not receiving antiretroviral therapy
* A change in antiretroviral therapy within 6 months of the start of screening (except if, after consultation with the sponsor, a change is made to avoid a potential drug-drug interaction with the study drug)
* Receiving antiretroviral therapy that may interfere with the study drug (consult the principal investigator \[PI\] for review of medication prior to enrollment)
* CD4 count \< 350 at screening
* An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening
